Chemical Constituents of the Fruits of Cornus Officinalis and Evaluation of their Neuroprotective Activity.

The phytochemical investigation of the fruits of Cornus officinalis yielded a new phenolic acid derivative, neophenolic acid A (1), and a novel flavonoid glycoside, (2R)-naringenin-7-O-ß-(6''-galloyl-glucopyranoside) (2 a), along with six known flavonoid glycosides (2 b-7). Their structures were determined by 1D, 2D NMR and HRESIMS data. The absolute configuration of 1 was established by ECD analysis. Compounds 1- 7 were evaluated for their neuroprotective activities against corticosterone (CORT)-induced injury in PC-12 cells. Compounds 1, 2 a, 2 b, 5, and 6 exhibited neuroprotective activities against CORT-induced neurotoxicity in PC-12 cells. The underlying mechanism study suggested that compounds 1, 2 a, 2 b, 5, and 6 were able to attenuate CORT-induced apoptosis and damage, increase the levels of MMP and decrease Ca2+ inward flow in PC-12 cells.

P-coumaric acid ameliorates Aß25-35-induced brain damage in mice by modulating gut microbiota and serum metabolites.

Alzheimer's disease (AD) is a progressive neurodegenerative disease for which there is a lack of effective therapeutic drugs. There is great potential for natural products to be used in the development of anti-AD drugs. P-coumaric acid (PCA), a small molecule phenolic acid widely distributed in the plant kingdom, has pharmacological effects such as neuroprotection, but its anti-AD mechanism has not been fully elucidated. In the current study, we investigated the mechanism of PCA intervention in the Aß25-35-induced AD model using gut microbiomics and serum metabolomics combined with in vitro and in vivo pharmacological experiments. PCA was found to ameliorate cognitive dysfunction and neuronal cell damage in Aß25-35-injected mice as measured by behavioral, pathological and biochemical indicators. 16S rDNA sequencing and serum metabolomics showed that PCA reduced the abundance of pro-inflammatory-associated microbiota (morganella, holdemanella, fusicatenibacter and serratia) in the gut, which were closely associated with metabolites of the glucose metabolism, arachidonic acid metabolism, tyrosine metabolism and phospholipid metabolism pathways in serum. Next, in vivo and in vitro pharmacological investigations revealed that PCA regulated Aß25-35-induced disruption of glucose metabolism through activation of PI3K/AKT/Glut1 signaling. Additionally, PCA ameliorated Aß25-35-induced neuroinflammation by inhibiting nuclear translocation of NF-κB and by modulating upstream MAPK signaling. In conclusion, PCA ameliorated cognitive deficits in Aß25-35-induced AD mice by regulating glucose metabolism and neuroinflammation, and the mechanism is related not only to restoring homeostasis of gut microbiota and serum metabolites, but also to PI3K/AKT/Glut1 and MAPK/NF-κB signaling.

Two new flavonoid thioglucosides from the seeds of Lepidium apetalum.

Two previously undescribed flavonoid thioglucosides lepidiumflavonosides A and B (1-2) and two known megastigmane compounds (7E,9S)-9-hydroxy-5,7-megastigmadien-4-one 9-O-ß-D-glucopyranoside (3) and (9S)-4-oxo-ß-inol ß-D-glucopyranoside (4) were isolated from the water extract of the seeds of Lepidium apetalum Willd. The structural elucidation of isolated compounds was unambiguously determined based on extensive 1D and 2D NMR spectroscopic analyses. All compounds were evaluated for their estrogen-like effects on MCF-7 cells in vitro. The results showed that compounds 1-4 significantly promoted the proliferation of MCF-7 cells, and the proliferation was antagonized by the specific ER antagonist ICI182,780, suggesting that compounds 1-4 might have the estrogen-like effect in vitro potentially.

Minor iridoid glycosides from the fruits of Cornus officinalis Sieb. et Zucc. and their anti-diabetic bioactivities.

Fifteen previously undescribed minor iridoid glycosides, including four monomers and eleven dimers, were isolated from the fruits of Cornus officinalis Sieb. et Zucc. Their chemical structures were determined on the basis of spectroscopic data and chemical evidence. All of the isolated compounds were evaluated for their effects of the glucose consumption on the insulin resistant HepG2 cells, and four compounds, named cornuofficinalisides F, H, L, and O, increased the glucose consumption significantly at 10 µM, the EC50 values of them were determined to be 0.898, 1.625, 0.923, and 8.589 µM, respectively. Moreover, the four compounds could improve the ability of glucose uptake significantly in insulin resistant HepG2 cells.

Four pairs of tautomers from rhizomes of Acorus calamus and fruits of Cornus officinalis.

A pair of new guaiane-type sesquiterpene tautomers (1) was isolated from rhizomes of Acorus calamus. Meanwhile, three pairs of known compounds, including a pair of dihydroflavone glycoside tautomers (2), a pair of 4-hydroxybenzoic acid ester glycoside tautomers (3), as well as a pair of secoiridoid glycoside tautomers (4) were isolated from fruits of Cornus officinalis. Their structures were elucidated by extensive spectroscopic and computational methods. Furthermore, the tautomeric mechanisms were discussed.

Alkaloids from the stem of Ephedra equisetina.

Two new cyclotrypyamine alkaloids equisetinines A and B, as well as three known alkaloids (3-5) were isolated from the stems of Ephedra equisetina Bunge. Their structures were characterized by spectroscopic methods, and the absolute configurations of the new compounds were determined by interpretation of their electronic circular dichroism. Anti-asthmatic activities of compounds were evaluated by releasing ß-Hex in C48/80-induced RBL-2H3 cells, and compound 5 exhibited significant anti-asthmatic activities.

Lignans and terpenoids from the stem of Ephedra equisetina Bunge.

Seven undescribed lignans, equiselignan A-F, and six undescribed terpenoids, equiseterpenoid A-E (including two pairs of enantiomers, (+/-)-equiselignan A and (+/-)-equiseterpenoid E), were isolated from the stems of Ephedra equisetina Bunge. Their structures were elucidated by spectroscopic methods, and the absolute configurations of the undescribed compounds were determined by interpretation of their electronic circular dichroic (ECD) and optical rotation data. In ß-hexosaminidase (ß-Hex) release assay, anti-asthmatic activities of all of the compounds were evaluated by releasing ß-Hex in C48/80-induced RBL-2H3 cells. The ß-Hex release rates of equiselignan B and equiseterpenoid B were 0.86 ± 0.094 and 0.86 ± 0.012 by comparing with model group, whereupon equiselignan B and equiseterpenoid B exhibited significant anti-asthmatic activities.

The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design.

Pyridine-based ring systems are one of the most extensively used heterocycles in the field of drug design, primarily due to their profound effect on pharmacological activity, which has led to the discovery of numerous broad-spectrum therapeutic agents. In the US FDA database, there are 95 approved pharmaceuticals that stem from pyridine or dihydropyridine, including isoniazid and ethionamide (tuberculosis), delavirdine (HIV/AIDS), abiraterone acetate (prostate cancer), tacrine (Alzheimer's), ciclopirox (ringworm and athlete's foot), crizotinib (cancer), nifedipine (Raynaud's syndrome and premature birth), piroxicam (NSAID for arthritis), nilvadipine (hypertension), roflumilast (COPD), pyridostigmine (myasthenia gravis), and many more. Their remarkable therapeutic applications have encouraged researchers to prepare a larger number of biologically active compounds decorated with pyridine or dihydropyridine, expandeing the scope of finding a cure for other ailments. It is thus anticipated that myriad new pharmaceuticals containing the two heterocycles will be available in the forthcoming decade. This review examines the prospects of highly potent bioactive molecules to emphasize the advantages of using pyridine and dihydropyridine in drug design. We cover the most recent developments from 2010 to date, highlighting the ever-expanding role of both scaffolds in the field of medicinal chemistry and drug development.

Development and preliminary testing of a probe-based duplex real-time PCR assay for the detection of African swine fever virus.

An outbreak of African swine fever (ASF) in China in 2018 caused substantial economic losses to the swine industry. To accurately diagnose clinical infection with ASF virus (ASFV), we developed a TaqMan probe-based duplex real-time PCR that simultaneously detected two discontinuous genes in the virus genome, thereby preventing the inaccurate results obtained with only one reaction. Two sets of ASFV gene-specific primers, along with two fluorescent TaqMan probes were designed to target conserved regions of the B646L and B438L genes. This method had high sensitivity and specificity, with a limit of detection of 10 copies/µL, and it did not cross-react with the genomes of other viral pathogens that affect pigs (i.e., CSFV, PRRSV, PEDV, PRV, PPV and PCV2). Overall, 180 clinical samples from ASFV-infected pig farms were used to compare this method with a commercial kit, which yielded excellent consistency (98.3%). This new diagnostic method should greatly improve the efficiency of ASFV surveillance and reduce economic losses, providing benefits for both animal and public health.

Iridoid glycosides and lignans from the fruits of Gardenia jasminoides Eills.

Four previously undescribed iridoid glycosides, including two bis-iridoid glycosides, and three undescribed lignans, together with 16 known analogues, were isolated from the fruits of Gardenia jasminoides Eills. Their structures were elucidated on basis of spectroscopic methods, and the absolute configurations of three of the unknown compounds were determined by interpretation of their electronic circular dichroic (ECD) and [α] [Formula: see text] data. The α-glucosidase inhibitory effects of the isolated compounds were evaluated and all the compounds exhibited slightly inhibitory activity with the values of IC50 greater than 50 µM.

Solanrubiellin A, a hydroanthraquinone dimer with antibacterial and cytotoxic activity from Solanum lyratum.

A new hydroanthraquinone dimer derivative, solanrubiellin A, was isolated from the whole plants of Solanum lyratum. The structure of 1 was established through extensive NMR spectroscopy analysis, and the absolute configuration was elucidated by comparison of its experimental and calculated ECD spectra. Compound 1 showed antibacterial activity with MIC values of 2-10 µM against several Gram-positive bacteria. Compound 1 also demonstrated cytotoxic activity against human A549, HT-29 and HL-60 cell lines with IC50 values ranging from 2.06 to 9.35 µM.

Polycycloiridals with a Cyclopentane Ring from Iris tectorum.

Six new iridal-type triterpenoids containing an unprecedented cyclopentane ring, polycycloiridals E-J (1-6), were isolated from a large-scale re-extraction of Iris tectorum. A possible biosynthesis pathway is postulated. The known spirioiridotectal D (7) was also obtained in the current investigation, and its structure was unequivocally defined using X-ray diffraction data. Compound 7 suppressed LPS-activated NO production in the BV2 cell line with an IC50 value of 0.54 µM.

Lignans from the rhizomes of Iris tectorum.

Chemical examination of the ethanol extract of rhizomes of Iris tectorum led to the isolation and characterization of three new lignans, (7R,7'R,8S,8'S)-5'-methoxy-neo-olivil (1a), (7S,7'S,8R,8'R) -5'-methoxy-neo-olivil (1b), (7S,7'R,8S,8'S)-neo-olivil (2a), (7R,7'S,8R,8'R)-neo-olivil (2b), (7R,7'R,8S,8'S,7''S,8''S)-threo-neo-olivil-4'-O-8-guaiacylglycerol ether (3), together with six known ones (4-9). Among them, compounds 1 and 2 were found to be racemic mixtures, respectively, which were verified by chiral HPLC analysis, compound 3 was a new sesquineolignan. The structures were elucidated on the basis of extensive spectroscopic analysis. To our knowledge, this is the first report of lignan constituents isolated from I. tectorum. All compounds were evaluated for their cytotoxicity against five human tumor cell lines and none of them displayed significant toxicity in tested cell lines at a concentration of 10 µM.

[Chemical Constituents from Eucommia ulmoides].

Objective: To investigate the chemical constituents from the barks of Eucommia ulmoides. Methods: After the reflux extraction of the barks of Eucommia ulmoides with 95% ethanol, and the ethyl acetate part was separated and purified by chromatographic methods, such as silica gel, Sephadex LH-20, and ODS C18. The structures of isolated compounds were elucidated with modern spectral methods. Results: Five lignanoids and three phenylpropanoids were isolated from Eucommia ulmoieds, which were confirmed as cycloolivil (1), (7R, 8S, 8'R)-4, 9, 4', 8'-tetrahydroxy-3, 3'-dimethyoxyl-7, 9'-monoepoxy lignan (2), erythro-guaiacyl-glycerol-ß-coniferyl aldehyde ether (3), pinonesinol (4), 8-hydroxypinoresinol (5), C-veratroylglycol (6), ß-hydroxyl-3-methoxyl-4-hydroxyacetophenone (7) and 3-hydroxy-4-methoxycinnamaladehyde (8). Conclusion: Compounds 5­8 are isolated from this plant for the first time.

Polycycloiridals A-D, Four Iridal-Type Triterpenoids with an α-Terpineol Moiety from Iris tectorum.

Polycycloiridals A-D, four novel iridals with an unprecedented α-terpineol moiety resulting from cyclization of the homofarnesylside chain, were isolated from the ethanol extract of rhizomes of Iris tectorum. Their structures were elucidated on the basis of comprehensive spectroscopic analysis. The absolute configuration of 1 was determined by the modified Mosher's method and comparison of experimental and calculated electronic circular dichroism (ECD) spectrum. A possible biosynthetic pathway was postulated.

[Flavonol glycosides from Lysimachia clethroides].

Eleven flavonol glycosides were isolated from the ethanol extract of Lysimachia clethroides by a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, and reversed-phase HPLC. Their structures were identified as astragalin (1), isoquercitrin (2), isorhamnetin-3-O-ß-D-glucopyranoside (3), quercetin-3-O-ß-D-6"-acetylglucopyranoside (4), quercetin-7-O-ß-D-glucopyranoside (5), prunin (6), 2-hydroxynaringin-5-O-ß-D-glucopyranoside (7), kaempferol-3-O-rutinonoside (8), kaempferol-3-O-robinobioside (9), rutin (10) and kaempferol-3,7-di-O-ß-D-glucopyranoside (11). Among them, compounds 4, 7 and 11 were obtained from the Lysimachia genus for the first time, while compounds 3, 5 and 9 were firstly reported from this plant. In the preliminary assays, compounds 2, 6 and 8 possessed significant inhibition against aldose reduc- tase, with IC50 values of 2.69, 1.00, 1.80 µmol · L(-1), respectively; none of compounds 1-11 exhibited obvious cytotoxic activity (IC50 > 10 µmol · L(-1)).

Sinensioside A, a new sesquilignan glycoside from Selaginella sinensis.

AIM: To investigate the chemical constituents of Selaginella sinensis (Desv.) Spring. METHODS: Chromatographic separations on Diaion HP-20, silica gel, and Sephadex LH-20 were used. The structures of the isolates were elucidated on the basis of spectroscopic analysis, as well as chemical methods. RESULTS: Eight compounds were obtained and their structures were identified as sinensioside A (1), syringaresinol-4- O-ß-D-glucopyranoside (2), (+)-medioresinol-4-O-ß-D-glucopyranoside (3), pinoresinol-4, 4'-di-O-ß-D-glucopyranoside (4), quercetin (5), eucomic acid (6), shikimic acid (7), and 2, 3-dihydroamentoflavone (8). CONCLUSION: Compound 1 is a new dihydrobenzofuran sesquilignan glycoside from Selaginella sinensis.

Ionone glycosides from the roots of Rehmannia glutinosa.

Four new ionone and ionone glycosides (1-4), and a new monoterpene (5), together with 10 known analogues (6-15), were isolated from the air-dried roots of Rehmannia glutinosa. The structures of these compounds were elucidated on the basis of spectroscopic data analysis. Furthermore, in in vitro assays, compound 3 (10 µM) exhibited moderate hepatoprotective activities against d-galactosamine-induced HL-7702 cell damage.

[Chemical constituents from fruit of Panax ginseng].

OBJECTIVE: To investigate chemical constituents from the ripe fruit of Panax ginseng. METHODS: The compounds were isolated and purified by chromatographic methods such as macroporous resin, sephadex LH-20, Bio-gel P-2, ODS and silica gel. Their structures were identified by their physical and spectral data(ESI-MS, 1H-NMR and 13C-NMR). RESULTS: Eleven compounds were isola- ted and identified as arginyl-fructose (1), arginyl-fructosyl-glucose (2), L-pyroglutamic acid (3), p-hydroxybenzoic acid (4), 5-hydroxy-methylfuraldehyde (5), ginsenosides Rb1 (6), Re (7), Rg1 (8), Rb2 (9), Rc (10) and daucosterol (11). CONCLUSION: Compounds 1-5 were obtained from the fruit of Panax ginseng for the first time.

Hepatoprotective triterpenoids and saponins of Schefflera kwangsiensis.

Seven new triterpenoid saponins, schekwangsiensides A-G (1-7), and a new triterpenoid, schekwangsienin (8), together with nine known triterpenoids and saponins (9-17), were isolated from the aerial parts of Schefflera kwangsiensis. The structures of these compounds were elucidated on the basis of spectroscopic data analysis and chemical evidence. Furthermore, in in vitro assays, compounds 4, 8, 9, and 15 (10 µM) exhibited moderate hepatoprotective activities against D-galactosamine-induced HL-7702 cell damage.